To realize high-quality vascularized bone regeneration, we developed a multifunctional hydrogel (SHPP-ZB) by incorporating BMP-2@ZIF-8/PEG-NH2 nanoparticles (NPs) into a sodium alginate/hydroxyapatite/polyvinyl alcohol hydrogel loaded with PDGF-BB, allowing for the sequential release of angiogenic and osteogenic growth factors (GFs) during bone repair. ZIF-8 served as a protective host for BMP-2 from degradation, ensuring high encapsulation efficiency and long-term bioactivity. The SHPP-ZB hydrogel exhibited enhanced mechanical strength and injectability, making it suitable for complex bone defects. It provided a swelling interface for tissue interlocking and the early release of Zn2+ and tannin acid (TA) to exert antioxidant and antibacterial effects, followed by the sequential release of angiogenic and osteogenic GFs to promote high-quality vascularized bone regeneration. In vitro experiments demonstrated the superior angiogenic and osteogenic properties of SHPP-ZB compared to other groups. In vivo experiments indicated that the sequential delivery of GFs via SHPP-ZB hydrogel could improve vascularized bone regeneration. Further, RNA sequencing analysis of regenerative bone tissue revealed that SHPP-ZB hydrogel promoted vascularized bone regeneration by regulating JUN, MAPK, Wnt, and calcium signaling pathways in vivo. This study presented a promising approach for efficient vascularized bone regeneration in large-scale bone defects.

中文翻译：

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ZIF-8 修饰的水凝胶依次传递血管生成和成骨生长因子，以加速血管化骨再生


为了实现高质量的血管化骨再生，我们通过将 BMP-2@ZIF-8/PEG-NH2 纳米颗粒 (NPs) 加入到负载有 PDGF-的海藻酸钠/羟基磷灰石/聚乙烯醇水凝胶中，开发了一种多功能水凝胶 (SHPP-ZB)。 BB，允许在骨修复过程中顺序释放血管生成和成骨生长因子（GF）。 ZIF-8 作为 BMP-2 免遭降解的保护宿主，确保高封装效率和长期生物活性。 SHPP-ZB水凝胶表现出增强的机械强度和可注射性，使其适用于复杂的骨缺损。它为组织连锁提供了一个膨胀界面，并早期释放Zn2+和单宁酸（TA）以发挥抗氧化和抗菌作用，随后依次释放血管生成和成骨GF以促进高质量的血管化骨再生。体外实验证明，与其他组相比，SHPP-ZB 具有优越的血管生成和成骨特性。体内实验表明，通过 SHPP-ZB 水凝胶顺序递送 GF 可以改善血管化骨再生。此外，再生骨组织的RNA测序分析表明，SHPP-ZB水凝胶通过调节体内JUN、MAPK、Wnt和钙信号通路促进血管化骨再生。这项研究提出了一种在大规模骨缺损中有效进行血管化骨再生的有前途的方法。